Myocardial infarction or chronic cardiomyopathies can cause irreversible damage to the cardiac tissue. Recent evidence for multipotent cardiovascular stem cells has raised expectations that these cells may be engaged to heal the injured myocardium. However, the biological properties of cardiovascular stem cells are poorly understood, we know little about how disease limits the regenerative potential of stem cells and, we lack pharmaceuticals to guide stem cells toward forming new cardiac tissue. To address these issues, the Vanderbilt University Hub proposes three interacting projects (P1-P3), a Hub Core and a Consortium-wide Bioinformatics Core. PI will focus on the role of adult progenitor cells in normal cardiac homeostasis and after ischemic injury. P2 will explore the regenerative potential of endocardial progenitor cells. Whereas P3 will investigate how the disease environment affects the fate of progenitor cells in the heart. We have designed a pilot study to screen small molecular libraries for compounds that Induce endocardial and myocardial differentiation. Positive hits will be evaluated for effects on cardiac stem cells and myocardial repair. The Hub structure also incorporates a Core for standardized mouse models of myocardial injury and assessment of cardiac histology and function. Finally, we propose a Bioinformatics Core to organize Consortium data into a Stem Cell database to accelerate discovery, strength the connections between Consortium partners and facilitate the dissemination of information to the scientific community and the public. The Vanderbilt Hub will create a dynamic and interactive network of investigators to advance our knowledge about the biology of cardiovascular progenitor cells and their role in cardiac tissue repair. The proposed experiments will lead to novel molecular and cellular tools for the therapy of cardiovascular diseases.